PROJECT SUMMARY The COVID-19 pandemic represents the most significant environmental event in living history and is leading to unprecedented social, economic and health consequences. There is an urgent need to longitudinally study the impact of the pandemic on pregnant women and the care they receive, and to understand the consequences for their children's birth outcomes and neurobehavioral development. Importantly, women with pre-existing substance use, mental health conditions and limited economic resources may be at increased risk for the wide- ranging, deleterious sequelae of the pandemic. The proposed project seeks to address these critical gaps by building upon ongoing harmonized research efforts across seven geographically-representative sites from the NIH HEALthy Brains and Cognitive Development study (HBCD) initiative, including New York University, Oregon Health Sciences University, Washington University in St. Louis, University of Pittsburgh, Cedars Sinai Medical Center, University of Vermont and Northwestern University. We will enroll pregnant and postpartum women into a multi-wave study in which we assess medical, economic, psychosocial and substance use risk across pregnancy and the perinatal period, studying associations of these factors to infant neurobehavioral development during the first year of life. Our central hypotheses include: 1) individual variation in perinatal COVID-19 related stress leads to differences in birth outcomes, parenting stress and infant temperament and neurodevelopment and 2) substance use, mental health and economic risk enhance susceptibility to negative COVID-19 related health and psychosocial outcomes. To pursue these aims, prospective longitudinal survey, birth and postpartum data will be obtained across a 3-month period in N=100 pregnant and new mothers per site (providing a total consortium sample of N=700) to generate individual temporal profiles of COVID-19 related experiences and responses, comparing outcomes with existing data from maternal-infant cohorts obtained prior to the pandemic. Further, to identify avenues for intervention, will evaluate substance use, poor mental health and low social economic status as risk factors and coping, agency and utilization of resources as resilience factors that influence COVID-19 related maternal stress and child health and neurobehavioral outcomes. The effects of geographic location will be used to examine the influence of pandemic severity, variation in local government policies and resource availability on these outcomes. Finally, we will collect and bank longitudinal perinatal biospecimens in N=40 women per site that will provide a foundation for future studies to evaluate the biological mechanisms through which the effects on maternal psychological and physical health influence offspring brain and behavioral development. Through this analysis of COVID-19 related stress, contextual factors and child outcomes, we will develop comprehensive understanding of effects and modifiers of this event on health outcomes in individuals that vary in dispositional risk during perinatal life, one of the most sensitive timepoints in human development.